Using a Parasite to Fight Cancer

Geisel researchers use Toxoplasma gondii to stimulate the body's own immune system to attack melanoma

Instead of removing tumors surgically, can we inject them with a "poison" that would cause them to destroy themselves? Scientists experiment in the lab with ways to use a common parasite in future treatment for cancer.

Toxoplasma gondii, the parasite that causes toxoplasmosis, is being used by Geisel researchers as a possible way to stimulate the immune system against tumors.

The idea of using the body's immune system to fight cancer is not a new one, but researchers are just now beginning to see the fruits of this idea in the lab—and hopefully soon in the clinic. "As tumor immunologists, we recognize that there is a revolution underway," says Steven Fiering, PhD, an immunologist at The Geisel School of Medicine at Dartmouth. "Historically, there have been three main approaches to treating cancer: radiation, surgery, and chemotherapy. Immunotherapy is becoming the fourth leg."

In a recent study published in the Journal of Immunology, Fiering and a number of colleagues in Geisel School of Medicine's Department of Microbiology and Immunology used a weakened strain of Toxoplasma gondii, a parasitic protozoan responsible for the disease toxoplasmosis, as an adjuvant to increase the effectiveness of a melanoma tumor vaccine.

The study used a safe strain of T. gondii developed by Barbara Fox and David Bzik, Geisel immunologists and coauthors of the study. Like normal T. gondii, this strain enters host cells and stimulates a strong immune response, but it is unable to replicate once inside the body and, after about a week, the nonreplicating parasites were eliminated by the immune system.

Lab research could be used in the clinic to treat melanoma cancer that returns after surgery

Fiering says it's possible the approach they used in the lab could be used directly in the clinic for melanoma. If a tumor recurs after it has been removed surgically it can be very difficult to eradicate. "Our idea would be, instead of surgically removing the tumor, to inject an immunostimulatory set of agents, one of which could be the T. gondii strain, thus stimulating the immune system to attack the tumor," Fiering says.

Toxoplasma gondii could be used for personalized approach to other cancers

In collaboration with Fiering, Bzik led a related study in which the research team examined the use of T. gondii as an ovarian cancer vaccine treatment. Fiering says the current treatment for ovarian cancer is to surgically debulk the tumor, and then use chemotherapy. This usually results in a remission for one to two years, at which point the tumor often recurs but is much more difficult to successfully treat.

The researchers are working on approaches that could perhaps take the tumor at the time of surgery and make it into a tumor vaccine by including the T. gondii to help stimulate the immune system to attack the tumor when it shows up again. This is a very personalized approach, because it uses each individual's tumor cells, and thus it is less convenient than a drug that can be used off the shelf. However, say Fiering and Bzik, it's a promising possibility because it can work very powerfully against tumors and may be effective in the clinic.

"Everything in the immune system is in a balance," says Fiering. "If we can upset the balance in the tumor that is immunosuppressive and make it immunostimulatory—once that release has happened, system-wide immunity can develop. We get a response in the lymph nodes and throughout the system." Bzik adds, "In laboratory tests this Toxoplasma treatment has the ability to completely cure established tumors and to then prevent their recurrence."